SOLUTION STRUCTURE OF MAUROTOXIN, A SCORPION TOXIN FROM SCORPIO-MAURUS, WITH HIGH-AFFINITY FOR VOLTAGE-GATED POTASSIUM CHANNELS

Maurotoxin (MTX), purified from the scorpionid Scorpio maurus is a pot ent ligand for potassium channels, It shows a broad specificity as bei ng active on Kv1.1 (Kd = 37 nM), Kv1.2 (Kd = 0.8 nM), Kv1.3 (Kd = 150 nM) voltage-gated potassium channels, as well as on small-conductance calcium-activated potassium channels, It has a unique disulfide pairin g among the scorpion toxins family, The solution structure of MTX has been determined by SD-NMR techniques, which led to the full descriptio n of its 3D conformation: a bended helix from residues 6 to 16 connect ed by a loop to a two-stranded antiparallel beta sheet (residues 23 to 26 and 28 to 31). The interaction of MTX with the pore region of the Kv1.2 potassium channel has been modeled according to their charge ani sotropy. The structure of MTX is similar to other short scorpion toxin s despite its peculiar disulfide pairing, Its interaction with the Kv1 .2 channel involves a dipole moment, which guides and orients the toxi n onto the pore, toward the binding site, and which thus is responsibl e for the specificity. (C) 1997 Wiley-Liss, Inc.